TAS-103 is a dual inhibitor of DNA topoisomerase I/II, used for cancer research.
TAS-103 is a dual inhibitor of DNA topoisomerase I/II. TAS-103 (0.1-10 μM) is active on CCRF-CEM cells, with an IC50 value of 5 nM. TAS-103 (0.1 μM) significantly increases levels of topo IIα FITC immunofluorescence in individual CCRF-CEM cells[1]. TAS-103 (0.01-1 μM) is highly cytotoxic to Lewis lung carcinoma (LLC) cells, and Liposomal TAS-103 is almost as active as free TAS-103[2]. TAS-103 inhibits the viability of HeLa cells, with an IC50 of 40 nM. TAS-103 (10 μM) disrupts signal recognition particle (SRP) complex formation, and induces destabilization of SRP14 and SRP19 and its eventual degradation[3].
TAS-103 (30 mg/kg, i.v.) causes significant tumor growth suppression in mice bearing Lewis lung carcinoma (LLC) cells, without obvious body weight loss, and the liposomal TAS-103 is more active than free TAS-103[2].
[1]. Padget K, et al. An investigation into the formation of N- [2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) and 6-[2-(dimethylamino)ethylamino]- 3-hydroxy-7H-indeno[2, 1-C]quinolin-7-one dihydrochloride (TAS-103) stabilised DNA topoisomerase I and II cleavable complexes in human leukaemia cells. Biochem Pharmacol. 2000 Sep 15;60(6):817-21. [2]. Shimizu K, et al. Cancer chemotherapy by liposomal 6-[12-(dimethylamino)ethyl]aminol-3-hydroxy-7H-indeno[2,1-clquinolin-7-one dihydrochloride (TAS-103), a novel anti-cancer agent. Biol Pharm Bull. 2002 Oct;25(10):1385-7. [3]. Yoshida M, et al. A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one dihydrochloride (TAS-103) action discovered by target screening with drug-immobilized affinity beads. Mol Pharmacol. 2008 Mar;73(3):987-94. Epub 2007 Dec 18.

TAS-103 acts as a dual inhibitor of DNA topoisomerase I and II, demonstrating potency across various cell lines. Specifically, it shows activity against CCRF-CEM cells within a concentration range of 0.1-10 μM, achieving an IC50 of 5 nM, and notably enhances topo IIα FITC immunofluorescence at a concentration of 0.1 μM[1]. It exhibits pronounced cytotoxic effects on Lewis lung carcinoma (LLC) cells across a 0.01-1 μM concentration range, with both its liposomal and free forms displaying nearly equivalent activity[2]. Additionally, TAS-103, at an IC50 of 40 nM, significantly reduces the viability of HeLa cells. At a concentration of 10 μM, it interferes with signal recognition particle (SRP) complex formation, leading to the destabilization and degradation of SRP14 and SRP19 proteins[3].

TAS-103 (30 mg/kg, i.v.) significantly suppresses tumor growth in mice with Lewis lung carcinoma (LLC) cells without causing noticeable loss of body weight. Furthermore, liposomal TAS-103 demonstrates greater efficacy than its free form[2].

CCRF-CEM human acute lymphoblastic leukaemia cells are grown in RPMI-1640 supplemented with 3 mM l-glutamine, 10% foetal bovine serum, 50 U/mL of penicillin, and 40 μg/mL of streptomycin at 37°C in a humidified atmosphere containing 5% CO2. TAS-103, CPT and DACA are dissolved in DMSO. Exponentially growing cells (～5 × 105) are exposed to either of the drugs for 2 hrs. Following drug exposure, cells are washed twice by centrifugation (400 × g, 3 min) in cold phosphate-buffered saline[1].